Systems and Methods for Cooling in a Thermal Cycler

Abstract

A device for performing polymerase chain reactions using cooling members not used in conventional thermal cyclers. A device for performing polymerase chain reactions may include a sample holder configured to receive a nucleic acid sample, a heating system configured to raise the temperature of the sample, a cooling system configured to lower the temperature of the sample, and a controller configured to operably control the heating system and the cooling system to cycle the device through a desired time-temperature profile. The cooling system may comprise at least one cooling member selected from a synthetic jet ejector array, a vibration-induced droplet atomization system, a vibrating diaphragm system, a piezo fan, a Cold Gun, a microchannel cooling loop, and a Cool Chip.

1 . A device for performing biological sample processing, the device comprising: 
 a sample holder configured to receive a biological sample;    a heating system configured to raise the temperature of the sample;    a cooling system configured to lower the temperature of the sample, wherein the cooling system comprises at least one cooling member; and    a controller configured to operably control the heating system and the cooling system to cycle the device through a desired time-temperature profile.    
     
     
         2 . The device of  claim 1 , further comprising: 
 a sample block configured to be placed in thermal contact with the sample holder; and    a heat sink associated with the sample block,    wherein the heating system is configured to raise the temperature of at least a portion of the sample block, and    wherein the cooling system is configured to lower the temperature of at least a portion of the sample block and to lower the temperature of ambient air being directed toward the heat sink.    
     
     
         3 . The device of  claim 2 , wherein the sample block comprises at least one recess configured to receive the sample holder.  
     
     
         4 . The device of  claim 2 , further comprising a thermoelectric device positioned between the sample block and the heat sink.  
     
     
         5 . The device of  claim 1 , wherein the at least one cooling member comprises a vibrating diaphragm system.  
     
     
         6 . The device of  claim 1 , wherein the at least one cooling member comprises a vibration-induced droplet atomization system.  
     
     
         7 . The device of  claim 1 , wherein the at least one cooling member comprises a piezo fan.  
     
     
         8 . The device of  claim 1 , wherein the at least one cooling member comprises a micro channel liquid cooling system.  
     
     
         9 . The device of  claim 1 , wherein the at least one cooling member is configured to direct one of carbon dioxide, liquid nitrogen, a chilled gas, and pressurized air into ambient air used for cooling the sample.  
     
     
         10 . The device of  claim 1 , wherein the cooling system and the heating system comprise an integral system.  
     
     
         11 . The device of  claim 1 , wherein the device is configured to perform polymerase chain reactions in a nucleic acid sample.  
     
     
         12 . The device of  claim 1 , wherein the sample holder is configured to respectively support plural amounts of the biological sample at a plurality of locations of the sample holder.  
     
     
         13 . A device for performing biological sample processing, the device comprising: 
 a sample holder configured to receive a biological sample;    a heating system configured to raise the temperature of the sample;    a cooling system configured to lower the temperature of the sample, wherein the cooling system comprises at least one cooling member selected from a synthetic jet ejector array, a vibration-induced droplet atomization system, a vibrating diaphragm system, a piezo fan, a Cold Gun, a microchannel cooling loop, and a Cool Chip; and    a controller configured to operably control the heating system and the cooling system to cycle the device through a desired time-temperature profile.    
     
     
         14 . The device of  claim 13 , further comprising: 
 a sample block configured to be placed in thermal contact with the sample holder; and    a heat sink associated with the sample block,    wherein the heating system is configured to raise the temperature of at least a portion of the sample block, and    wherein the cooling system is configured to lower the temperature of at least a portion of the sample block and to lower the temperature of ambient air being directed toward the heat sink.    
     
     
         15 . The device of  claim 14 , wherein the sample block comprises at least one recess configured to receive the sample holder.  
     
     
         16 . The device of  claim 14 , further comprising a thermoelectric device positioned between the sample block and the heat sink.  
     
     
         17 . The device of  claim 14 , wherein the at least one cooling member is configured to output a cooling fluid.  
     
     
         18 . The device of  claim 17 , wherein the cooling fluid comprises one of carbon dioxide, liquid nitrogen, and compressed air.  
     
     
         19 . The device of  claim 17 , further comprising a network of plumbing and valves configured to direct the cooling fluid from the at least one cooling member toward a region of the heat sink.  
     
     
         20 . The device of  claim 17 , wherein the at least one cooling member is configured to direct the fluid toward a region of the heat sink.  
     
     
         21 . The device of  claim 14 , wherein the heat sink comprises cooling fins, and the at least one cooling member is mounted within the cooling fins.  
     
     
         22 . The device of  claim 13 , wherein the controller is configured to operably control the cooling system to achieve a predetermined temperature gradient among at least some of the samples.  
     
     
         23 . The device of  claim 13 , wherein the device is configured to perform polymerase chain reactions.  
     
     
         24 . The device of  claim 13 , wherein the sample holder is configured to respectively support plural amounts of the biological sample at a plurality of locations of the sample holder.  
     
     
         25 . The device of  claim 13 , wherein the biological sample comprises a nucleic acid sample.  
     
     
         26 . A device for performing biological sample processing, the device comprising: 
 means for holding a biological sample;    means for heating the sample;    means for cooling the sample, wherein the means for cooling the sample comprises a heat sink and a means for cooling the heat sink, wherein the means for cooling the heat sink comprises a cooling member; and    means for controlling the means for heating and the means for cooling to cycle the device through a desired time-temperature profile.    
     
     
         27 . The device of  claim 26 , wherein the biological sample comprises a nucleic acid sample and wherein the device is configured to perform polymerase chain reactions.  
     
     
         28 . A device for biological sample processing, the device comprising: 
 an enclosure configured to receive a biological sample for processing;    a heat sink in thermal communication with the enclosure; and    a thermal system configured to modulate a temperature of the at least one biological sample, the thermal system comprising a cooling system configured to lower a temperature of the at least one biological sample,    wherein the cooling system comprises a cooling fluid output configured to flow cooling fluid into a plurality of flow structures configured to respectively direct the cooling fluid to a plurality of differing locations of the heat sink, the cooling fluid being configured to absorb heat at the plurality of differing locations.    
     
     
         29 . The device of  claim 28 , wherein the cooling fluid comprises at least one of air, water, a chilled gas, and carbon dioxide.  
     
     
         30 . The device of  claim 28 , wherein the plurality of flow structures comprise flow channels.  
     
     
         31 . The device of  claim 28 , further comprising a thermoelectric device in thermal communication with the enclosure.  
     
     
         32 . The device of  claim 28 , wherein the enclosure is configured to receive a sample holder for holding plural amounts of the biological sample.  
     
     
         33 . The device of  claim 32 , wherein the enclosure is configured to receive a sample holder comprising one of a microtiter plate, a microcard, a plurality of capillaries, and a plurality of tubes.  
     
     
         34 . The device of  claim 28 , further comprising a sample holder configured to hold the biological sample for processing.  
     
     
         35 . The device of  claim 34 , wherein the sample holder comprises one of a microtiter plate, a microcard, a plurality of capillaries, and a plurality of tubes.  
     
     
         36 . The device of  claim 28 , further comprising a cover configured to form at least part of the enclosure.  
     
     
         37 . The device of  claim 28 , further comprising a sample block configured to form at least part of the enclosure and to support the biological sample.  
     
     
         38 . The device of  claim 28 , wherein the sample block is configured to transfer heat with the biological sample.  
     
     
         39 . The device of  claim 28 , wherein the biological sample comprises a nucleic acid sample and wherein the device is configured to perform polymerase chain reactions on the nucleic acid sample.  
     
     
         40 . The device of  claim 28 , further comprising a control system for controlling the thermal system.  
     
     
         41 . The device of  claim 28 , wherein the thermal system further comprises a heating system configured to raise a temperature of the at least one biological sample.  
     
     
         42 . The device of claim  284 , wherein the cooling system and the heating system comprise an integral system.  
     
     
         43 . The device of  claim 28 , wherein the heat sink comprises a plurality of projecting members configured to transfer heat away from the enclosure.  
     
     
         44 . The device of  claim 43 , wherein the plurality of projecting members comprise a plurality of fins.  
     
     
         45 . The device of  claim 43 , wherein the plurality of flow structures are configured to respectively direct the cooling fluid to differing groups of projecting members.  
     
     
         46 . The device of  claim 28 , wherein the cooling system comprises at least one of a synthetic jet ejector array, a vibration-induced droplet atomization system, a vibrating diaphragm system, a piezo fan, a Cold Gun, a microchannel cooling loop, and a Cool Chip.  
     
     
         47 . The device of  claim 28 , wherein the cooling system comprises a fan.  
     
     
         48 . A method for performing biological sample processing, the method comprising: 
 supplying an enclosure with a biological sample for processing within the enclosure;    modulating a temperature of the biological sample to cycle a temperature of the biological sample,    wherein modulating the temperature of the biological sample comprises respectively directing a cooling fluid via a plurality of separate flow passages to a plurality of locations of a heat sink in thermal communication with the enclosure, wherein the plurality of locations are independently cooled via the cooling fluid respectively directed to each of the plurality of locations.    
     
     
         49 . The method of  claim 48 , wherein supplying the enclosure comprises supplying a sample holder holding the biological sample to the enclosure.  
     
     
         50 . The method of  claim 49 , wherein supplying the sample holder comprises supplying one of a microtiterplate, a microcard, a plurality of capillaries, and a plurality of tubes holding the biological sample.  
     
     
         51 . The method of  claim 48 , wherein modulating the temperature of the biological sample comprises modulating the temperature via a thermoelectric device.  
     
     
         52 . The method of  claim 48 , wherein modulating the temperature of the biological sample further comprises heating the biological sample.  
     
     
         53 . The method of  claim 48 , wherein modulating the temperature of the biological sample further comprises controlling a temperature of a sample block in thermal communication with the biological sample.  
     
     
         54 . The method of  claim 48 , wherein directing the cooling fluid comprises directing a cooling fluid comprising one of air, water, a chilled gas, and carbon dioxide.  
     
     
         55 . The method of  claim 48 , further comprising performing polymerase chain reactions on the biological sample supplied to the enclosure.  
     
     
         56 . The method of  claim 48 , wherein supplying the enclosure with the biological sample for processing within the enclosure comprises supplying the enclosure with a nucleic acid sample.  
     
     
         57 . The method of  claim 48 , wherein directing the cooling fluid comprises directing a cooling fluid output from one of a synthetic jet ejector array, a vibration-induced droplet atomization system, a vibrating diaphragm system, a piezo fan, a Cold Gun, a microchannel cooling loop, and a Cool Chip.  
     
     
         58 . The method of  claim 48 , wherein modulating the temperature of the biological sample comprises circulating air from a fan to provide cooling.